Development of a cancer stem cell vaccine
Cancer stem cell (CSC) phenomenon may explain one of the reasons for the lack of effectiveness of current immunotherapies for cancer which mainly target the differentiated cancer cells. We identified CSC-enriched populations in histologically distinct murine tumors and evaluated their immunogenicity by administering CSC-dendritic cell (DC) based vaccines in genetically different syngeneic immunocompetent hosts. Enriched CSCs are immunogenic and significantly more effective as an antigen source compared with unselected tumor cells or enriched non-CSCs in inducing protective anti-tumor immunity. The CSC-based vaccines have conveyed significant protection against tumor challenge through selective immunological targeting of CSCs by CSC-primed antibodies and CTLs. We need to further define the immunological mechanisms by which CSC-vaccine induces antitumor immunity and to optimize its applications in cancer treatment. Translational work may represent a prelude to the initiation of clinical studies by evaluating the anti-CSC immune responses in human T and B cells induced by CSC-DC vaccines in vitro and in vivo. Together, the findings may demonstrate proof of principle that the findings in our animal models may be translated into clinical trials. This may lead to the development of innovative immunotherapy for human cancers by using an autologous CSC-DC vaccine to specifically target cancer stem cells.